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Autocrine TGF-β1 drives tissue-specific differentiation and function of resident NK cells

Group 1 innate lymphoid cells (ILCs) encompass NK cells and ILC1s, which have non-redundant roles in host protection against pathogens and cancer. Despite their circulating nature, NK cells can establish residency in selected tissues during ontogeny, forming a distinct functional subset. The mechani...

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Main Authors: Sparano, Colin (Author) , Solís-Sayago, Darío (Author) , Zangger, Nathan Sébastien (Author) , Rindlisbacher, Lukas (Author) , Van Hove, Hannah (Author) , Vermeer, Marijne (Author) , Westermann, Frederike (Author) , Mussak, Caroline (Author) , Rallo, Elisa (Author) , Dergun, Stanislav (Author) , Litscher, Gioana (Author) , Xu, Yishu (Author) , Bijnen, Mitchell (Author) , Friedrich, Christin (Author) , Greter, Melanie (Author) , Juranić Lisnić, Vanda (Author) , Becher, Burkhard (Author) , Gasteiger, Georg (Author) , Oxenius, Annette (Author) , Tugues, Sònia (Author)
Format: Article (Journal)
Language:English
Published: December 18 2024
In: Journal of experimental medicine
Year: 2024, Volume: 222, Issue: 3, Pages: 1-17, S1-7
ISSN:1540-9538
DOI:10.1084/jem.20240930
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1084/jem.20240930
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Author Notes:Colin Sparano, Darío Solís-Sayago, Nathan Sébastien Zangger, Lukas Rindlisbacher, Hannah Van Hove, Marijne Vermeer, Frederike Westermann, Caroline Mussak, Elisa Rallo, Stanislav Dergun, Gioana Litscher, Yishu Xu, Mitchell Bijnen, Christin Friedrich, Melanie Greter, Vanda Juranić Lisnić, Burkhard Becher, Georg Gasteiger, Annette Oxenius, and Sonia Tugues
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Summary:Group 1 innate lymphoid cells (ILCs) encompass NK cells and ILC1s, which have non-redundant roles in host protection against pathogens and cancer. Despite their circulating nature, NK cells can establish residency in selected tissues during ontogeny, forming a distinct functional subset. The mechanisms that initiate, maintain, and regulate the conversion of NK cells into tissue-resident NK (trNK) cells are currently not well understood. Here, we identify autocrine transforming growth factor-β (TGF-β) as a cell-autonomous driver for NK cell tissue residency across multiple glandular tissues during development. Cell-intrinsic production of TGF-β was continuously required for the maintenance of trNK cells and synergized with Hobit to enhance cytotoxic function. Whereas autocrine TGF-β was redundant in tumors, our study revealed that NK cell-derived TGF-β allowed the expansion of cytotoxic trNK cells during local infection with murine cytomegalovirus (MCMV) and contributed to viral control in the salivary gland. Collectively, our findings reveal tissue-specific regulation of trNK cell differentiation and function by autocrine TGF-β1, which is relevant for antiviral immunity.
Item Description:Gesehen am 22.04.2025
Physical Description:Online Resource
ISSN:1540-9538
DOI:10.1084/jem.20240930

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